7-OH-cannabidiol (7-OH-CBD) and/or 7-OH-cannabidivarin (7-OH-CBDV) for use in the treatment of epilepsy

ABSTRACT

The present invention relates to the use of 7-hydroxy-cannabidol (7-OH-CBD) and/or 7-hydroxy-cannabidivarin (7-OH-CBDV) in the treatment of epilepsy. Preferably the cannabinoid metabolites are isolated from plants to produce a highly purified extract or can be reproduced synthetically.

RELATED APPLICATIONS

This application is a Continuation of U.S. application Ser. No.15/321,819, filed Dec. 23, 2016, which is a national stage filing under35 U.S.C. § 371 of International Application No. PCT/GB2015/051894,filed Jun. 29, 2015, the entire disclosure of each of which isincorporated by reference herein in its entirety.

The present invention relates to the use of 7-hydroxy-cannabidol(7-OH-CBD) and/or 7-hydroxy-cannabidivarin (7-OH-CBDV) in the treatmentof epilepsy.

Preferably the cannabinoid metabolites are isolated from plants toproduce a highly purified extract or can be reproduced synthetically.

BACKGROUND TO THE INVENTION

Epilepsy occurs in approximately 1% of the population worldwide,(Thurman et al., 2011) of which 70% are able to adequately control theirsymptoms with the available existing anti-epileptic drugs (AED).However, 30% of this patient group, (Eadie et al., 2012), are unable toobtain seizure freedom from the AED that are available and as such aretermed as suffering from “treatment-resistant epilepsy” (TRE).

There are several different types of AED available to treat epilepsy,some of the most common AED defined by their mechanisms of action aredescribed in the following tables:

Examples of Narrow Spectrum AED

Narrow-spectrum AED Mechanism Phenytoin Sodium channel PhenobarbitalGABA/Calcium channel Carbamazepine Sodium channel Oxcarbazepine Sodiumchannel Gabapentin Calcium channel Pregabalin Calcium channel LacosamideSodium channel Vigabatrin GABA

Examples of Broad Spectrum AED

Broad-spectrum AED Mechanism Valproic acid GABA/Sodium channelLamotrigine Sodium channel Topiramate GABA/Sodium channel ZonisamideGABA/Calcium/Sodium channel Levetiracetam Calcium channel ClonazepamGABA Rufinamide Sodium channel

Individuals who develop epilepsy during the first few years of life areoften difficult to treat and as such are often termedtreatment-resistant. Children who undergo frequent seizures in childhoodare often left with neurological damage which can cause cognitive,behavioral and motor delays.

Childhood epilepsy is a relatively common neurological disorder inchildren and young adults with a prevalence of approximately 700 per100,000. This is twice the number of epileptic adults per population.

When a child or young adult presents with a seizure, investigations arenormally undertaken in order to investigate the cause. Childhoodepilepsy can be caused by many different syndromes and genetic mutationsand as such diagnosis for these children may take some time.

Childhood epilepsy refers to the many different syndromes and geneticmutations that can occur to cause epilepsy in childhood. Examples ofsome of these are as follows: Dravet Syndrome; Myoclonic-AbsenceEpilepsy; Lennox-Gastaut syndrome; Generalized Epilepsy of unknownorigin; CDKL5 mutation; Aicardi syndrome; bilateral polymicrogyria;Dup15q; SNAP25; and febrile infection related epilepsy syndrome (FIRES);benign rolandic epilepsy; juvenile myoclonic epilepsy; infantile spasm(West syndrome); and Landau-Kleffner syndrome. The list above isnon-exhaustive as many different childhood epilepsies exist.

Examples of AED Used Specifically in Childhood Epilepsy

AED Mechanism Clobazam GABA Stiripentol GABA

The International League Against Epilepsy (ILAE) in 2011 havereclassified the old terms of “general” and “partial” seizures”. The newterm “generalized seizure” refers to seizures conceptualized asoriginating at some point within the brain and rapidly engagingbilaterally distributed networks.

The new term “focal seizure” now refers to seizures conceptualized asoriginating at some point within the brain and being limited to onehemisphere.

The etiology of epilepsy has also been reclassified by the ILAE as beingof genetic origin; structural or metabolic origin; or of unknown origin.

There is also now no specific classification for focal seizure types,therefore the terms complex partial and simple partial seizure are nolonger in use.

There are several different animal models that can be used to test theefficacy of compounds as anti-convulsants. These include thepentylenetetrazole-induced (PTZ) model of generalised seizures and theMaximal Electroshock (MES) model of generalised seizures.

Over the past forty years there have been a number of animal studies onthe use of the non-psychoactive cannabinoid cannabidiol (CBD) to treatseizures. For example, Consroe et al., (1982) determined that CBD wasable to prevent seizures in mice after administration of pro-convulsantdrugs or an electric current.

Studies in epileptic adults have also occurred in the past forty yearswith CBD. Cunha et al. reported that administration of CBD to eightadult patients with generalized epilepsy resulted in a marked reductionof seizures in 4 of the patients (Cunha et al., 1980).

A study in 1978 provided 200 mg/day of pure CBD to four adult patients,two of the four patients became seizure free, whereas in the remainderseizure frequency was unchanged (Mechoulam and Carlini, 1978).

Carlini et al. in 1981 described a further study where CBD was providedto healthy volunteers, insomniacs and epileptic patients. Seven out ofthe eight epileptic patients described an improvement in theircondition.

In contrast to the studies described above, an open label study reportedthat 200 mg/day of pure CBD was ineffective in controlling seizures intwelve institutionalized adult patients (Ames and Cridland, 1986).

In the past forty years of research there have been over thirty drugsapproved for the treatment of epilepsy none of which are cannabinoids.Indeed, there appears to have been a prejudice against cannabinoids,possible due to the scheduled nature of these compounds and/or the factthat THC, which is a known psychoactive, has been ascribed as apro-convulsant (Consroe et al., 1977).

More recently the applicant has discovered that the cannabinoids CBD andCBDV are effective in animal models of epilepsy. For example EP2,448,637 describes the use of CBD in the treatment of partial seizuresand WO 2011/121351 describes the use of CBDV in the treatment ofepilepsy. Hill et al. (2012) and Amada et al. (2013) both also describethe use of CBDV in the treatment of epilepsy. Jones et al. (2012)describes the anti-convulsant activity of CBD in animal models.

Furthermore GB 2495118 describes the use of a pharmaceutical compositioncomprising a combination of CBDV and CBD.

The synthetic production of the metabolite of CBD,7-hydroxy-cannabidiol, (7-OH CBD) is disclosed in WO 01/95899 inaddition to many other CBD derivatives. The compound was tested in amodel of inflammation and found to be effective. The application goes onto suggest that the compound may be of use as an analgesic,anti-anxiety, anti-convulsant, neuroprotective, anti-psychotic andanti-inflammatory based on the mechanisms the compound displays in themodel of inflammation. However no data is presented to support the useof 7-OH-CBD as an anti-convulsant.

To date there have been no studies into the anti-convulsant effect ofmetabolites of CBD and CBDV.

Surprisingly, it has now been found that a metabolite of CBD,7-hydroxy-cannabidiol, (7-OH CBD) and a metabolite of CBD,7-hydroxy-cannabidivarin, (7-OH CBDV) are effective in the treatment ofepilepsy. The metabolites appear to be more effective than their parentcompounds in certain aspects of seizure control.

BRIEF SUMMARY OF THE DISCLOSURE

In accordance with a first aspect of the present invention there isprovided 7-hydroxy-cannabidivarin (7-OH-CBDV) in a pure, isolated orsynthetic form for use as a medicament.

In accordance with a second aspect of the present invention there isprovided 7-hydroxy-cannabidivarin (7-OH-CBDV) in a pure, isolated orsynthetic form for use in the treatment of epilepsy.

In accordance with a third aspect of the present invention there isprovided 7-hydroxy-cannabidol (7-OH-CBD) in a pure, isolated orsynthetic form for use in the treatment of epilepsy.

In one embodiment the 7-hydroxy-cannabidivarin (7-OH-CBDV) in a pure,isolated or synthetic form is used in combination with7-hydroxy-cannabidol (7-OH-CBD) in a pure, isolated or synthetic form.

In accordance with a fourth aspect of the present invention there isprovided a pharmaceutical composition comprising7-hydroxy-cannabidivarin (7-OH-CBDV) and/or 7-hydroxy-cannabidol(7-OH-CBD) with a pharmaceutically acceptable carrier.

In accordance with a fifth aspect of the present invention there isprovided a pharmaceutical composition comprising7-hydroxy-cannabidivarin (7-OH-CBDV) and/or 7-hydroxy-cannabidol(7-OH-CBD) with a pharmaceutically acceptable carrier for use in thetreatment of epilepsy.

In one embodiment the 7-hydroxy-cannabidol (7-OH-CBD) and/or7-hydroxy-cannabidivarin (7-OH-CBDV) are used in combination with one ormore concomitant anti-epileptic drugs (AED).

Preferably the one or more AED is selected from the group consisting of:clobazam; levetiracetam; topiramate; stiripentol; phenobarbital;lacsamide; valproic acid; zonisamide; perampanel; and fosphenytoin.

Preferably the dose of 7-OH-CBD and/or the 7-OH-CBDV is between 1 and2000 mg/kg.

Preferably the 7-OH-CBDV may be formulated for administrationseparately, sequentially or simultaneously with the 7-OH-CBD or thecombination may be provided in a single dosage form.

It is envisaged that the composition be administered as an oral liquidsolution. Other modes of administration including solids, semi-solids,gels, sprays, aerosols, inhalers, vaporisers, enemas and suppositoriesare alternative administration forms. Such medicaments could beadministered via the oral, buccal, sublingual, respiratory, nasal anddistal rectum route.

In accordance with a sixth aspect of the present invention there isprovided a method of treating epilepsy comprising administering atherapeutically effective amount of 7-hydroxy-cannabidiol (7-OH-CBD)and/or 7-hydroxy-cannabidivarin (7-OH-CBDV) to a subject in needthereof.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the invention are further described hereinafter withreference to the accompanying drawings, in which:

FIG. 1 shows CBDV and CBD, and their 7-OH metabolites in the PTZ modelof acute seizure.

LEGEND TO THE FIGURES

FIG. 1. CBDV and 7-OH CBDV were dosed at 200 mg/kg, and CBD and 7-OH CBDwere dosed at 100 mg/kg (A) Maximum observed seizure severity (medianseverity in grey, box represents interquartile range, whiskers representmaxima and minima; Kruskal-Wallis test, with a post-hoc Mann-Whitney U)(B) Mortality (Chi-squared test, with a post-hoc Fisher exact) (C)Animals exhibiting tonic-clonic seizures (Chi-squared test, with apost-hoc Fisher exact) (D) Latency to seizure onset (median withinterquartile range; Kruskal-Wallis test, with a post-hoc Mann-WhitneyU). n=11 for each dose, *=p≤0.05, **=p≤0.01.

Definitions

Definitions of some of the terms used to describe the invention aredetailed below:

The cannabinoids described in the present application are listed belowalong with their standard abbreviations.

CBD Cannabidiol

7-OH-CBD 7-hydroxy-cannabidiol

CBDV Cannabidivarin

7-OH-CBDV 7-hydroxy-cannabidivarin

The table above is not exhaustive and merely details the cannabinoidswhich are identified in the present application for reference. So farover 60 different cannabinoids have been identified and thesecannabinoids can be split into different groups as follows:Phytocannabinoids; Endocannabinoids and Synthetic cannabinoids (whichmay be novel cannabinoids or synthetically produced phytocannabinoids orendocannabinoids).

“Cannabinoid metabolites” are metabolites from cannabinoids thatoriginate when the parent cannabinoid is metabolised or broken down. Thecannabinoid metabolites can be isolated from plants to produce a highlypurified extract or can be reproduced synthetically.

“Highly purified cannabinoid metabolites” are defined as cannabinoidsthat have been extracted from the cannabis plant and purified to theextent that other cannabinoids and non-cannabinoid components that areco-extracted with the cannabinoids have been removed, such that thehighly purified cannabinoid is greater than 90%, more preferably greaterthan 95%, most preferably greater than 98% (w/w) pure.

The cannabinoid metabolites may be manufactured synthetically and/orproduced from the parent cannabinoid by enzymatic means.

Phytocannabinoids can be obtained as either the neutral (decarboxylatedform) or the carboxylic acid form depending on the method used toextract the cannabinoids. For example it is known that heating thecarboxylic acid form will cause most of the carboxylic acid form todecarboxylate into the neutral form.

The human dose equivalent (HED) can be estimated using the followingformula:

${H\; E\; D} = {{Animal}\mspace{14mu}{dose}\mspace{14mu}\left( {{mg}\text{/}{kg}} \right)\mspace{14mu}{multiplied}\mspace{14mu}{by}\mspace{14mu}\frac{{Animal}\mspace{14mu} K_{m}}{{Human}\mspace{14mu} K_{m}}}$The K_(m) for a rat is 6 and the K_(m) for a human is 37.Thus, for a human of approximately 60 Kg a 200 mg/Kg dose in rat wouldequate to a human daily dose of about 2000 mg.

DETAILED DESCRIPTION

The following Examples describe for the first time the anti-convulsantactivity of the metabolites of CBD, namely 7-OH-CBD and CBDV, namely,7-OH-CBDV.

Example 1: Efficacy of 7-Hydroxy Cannabidiol (7-Oh-Cbd) and 7-HydroxyCannabidivarin (7-Oh-Cbdv) in the Ptz Model of Seizure Materials andMethods Compounds

The compounds 7-OH CBD and 7-OH-CBDV have never been tested in a modelof epilepsy and as such the effects were examined at one dose level inorder to determine efficacy.

The hydroxy-metabolites of CBD and CBDV were also tested against theirparent cannabinoids which were used as positive controls. The tablebelow details the doses used in this study.

Compound Dose (mg/kg) Vehicle — CBDV 200 7-OH-CBDV 200 CBD 100 7-OH CBD100

General Methodology for PTZ Model Animals

Male Wistar rats (P24-29; 75-110 g) were used to assess the effects ofthe cannabinoids listed above on the PTZ model of generalised seizures.Animals were habituated to the test environment, cages, injectionprotocol and handling prior to experimentation. Animals were housed in aroom at 21° C. on a 12 hour light: dark cycle (lights on 0900) in 50%humidity, with free access to food and water.

Experimental Setup

Five 6 L Perspex® tanks with lids were placed on a single bench withdividers between them. Closed-circuit television (CCTV) cameras weremounted onto the dividers to observe rat behaviour. Sony Topica CCDcameras (Bluecherry, USA) were linked via BNC cables to a low-noise PCvia Brooktree digital capture cards (Bluecherry, USA). Zoneminder(http://www.zoneminder.com) software was used to monitor rats, start andend recordings and manage video files. In-house Linux® scripts were usedto encode video files into a suitable format for further offlineanalysis

Experimental Protocols

On the day of testing, animals received an IP injection with either thecannabinoids (or a matched volume of the cannabinoids vehicle (1:1:18ethanol:Cremophor: 0.9% w/v NaCl solution), which served as the negativecontrol group. Animals were then observed for 30 mins, after which timethey received an IP injection of 70 or 80 mg/kg PTZ. Negative vehiclecontrols were performed in parallel with cannabinoid-dosed subjects.After receiving a dose of PTZ, animals were observed and videoed todetermine the severity of seizure and latency to several seizurebehaviour types (see in vivo analysis, below). Animals were filmed forhalf an hour after last sign of seizure, and then returned to theircage.

In Vivo Analysis

Animals were observed during experimental procedures, but all analysiswas performed offline on recorded video files using The Observerbehavioural analysis software (Noldus, Netherlands). A seizure severityscoring system was used to determine the levels of seizure experiencedby subjects (Table 1). All signs of seizure were detailed for allanimals.

TABLE 1 Seizure severity scoring scale Seizure Righting scoreBehavioural expression reflex 0 No changes to behaviour Preserved 0.5Abnormal behaviour (sniffing, Preserved excessive washing, orientation)1 Isolated myoclonic jerks Preserved 2 Atypical clonic seizure Preserved3 Fully developed bilateral Preserved forelimb clonus 3.5 Forelimbclonus with tonic Preserved component and body twist 4 Tonic-clonicseizure with Lost suppressed tonic phase 5 Fully developed tonic-clonicLost seizure 6 Death

Latency From Injection of PTZ to Specific Indicators of SeizureDevelopment

The latency (in seconds) from injection of PTZ to first myoclonic jerk(FMJ; score of 1), and to the animal attaining “forelimb clonus withtonic component and body twist” (score of 3.5) were recorded. FMJ is anindicator of the onset of seizure activity, whilst >90% of animalsdeveloped scores of 3.5, and so is a good marker of the development ofmore severe seizures. Data are presented as the mean±S.E.M. within anexperimental group.

Maximum Seizure Severity

This is given as the median value for each experimental group based onthe scoring scale above.

Percentage Mortality

The percentage of animals within an experimental group that died as aresult of PTZ-induced seizures. A score of 6 (death) automaticallydenotes that the animal also experienced tonic-clonic seizures.

Seizure Duration

The time (in seconds) from the first sign of seizure (typically FMJ) toeither the last sign of seizure or, in the case of subjects that died,the time of death—separated into animals that survived and those thatdid not. This is given as the mean±S.E.M. for each experimental group.

Statistics

Differences in latencies and durations were assessed by one-way analysisof variance (ANOVA) with post-hoc Tukey's test. P≤0.05 was consideredsignificant.

Results

FIG. 1A shows that treatment with all of the compounds, both parents andmetabolites resulted in a decrease the observed maximum seizureseverity. CBDV significantly reduced seizure severity (p≤0.01).

FIG. 1B shows that CBDV and 7-OH-CBDV had a significant effect onmortality of the animals. There was also a reduction in mortalityobserved for CBD and 7-OH-CBD.

FIG. 1C demonstrates that the incidence of tonic clonic seizures wassignificantly reduced by CBDV and to a lesser extent 7-OH-CBDV.

FIG. 1D demonstrates that the latency to the onset of seizures was alsoaffected by the administration of cannabinoids. Indeed 7-OH CBDsignificantly reduced the latency to seizure onset (p≤0.01).

Conclusions

These results demonstrate that both 7-OH-CBD and 7-OH-CBDV showanti-convulsant action in the PTZ model of acute seizure.

Furthermore the ability 7-OH-CBD to significantly reduce the latency toonset of seizures and of 7-OH-CBDV to significantly reduce the medianseizure severity, from 5 to 3 are remarkable as these data infer thatthe metabolites may be more effective than their parent compounds incertain aspects of seizure control.

The fact that the 7-OH-CBD and 7-OH-CBDV appear to be more potent thantheir parent cannabinoids, CBD and CBDV respectively, means that lowerdoses of the metabolites may be used in the treatment of epilepsy.

Example 2: Efficacy of 7-Hydroxy Cannabidivarin (7-Oh-Cbdv) in theMaximal ELECTROSHOCK (MES) MODEL OF SEIZURE Preparation of Test andReference Compounds

The vehicle used in this study was 2:1:17 (ethanol:Cremophor:0.9% w/vNaCl). The test compound used was 7-OH-CBDV. This was made to a solutionat the highest concentration; then dissolved in ethanol beforecombination with Cremophor and 0.9% NaCl in the proportion describedabove. The 7-OH-CBDV was administered intraperitoneally at a volume of10 ml/kg body weight.

Test System

Animal Species/Strain: Mouse/ICR, Microbiological grade: SPF, Inc. Sex:male, Age (at time of testing): 5-7 weeks old, Number of animals: about5 animals per group. Temperature: 23±2° C., Humidity: 60±10%, Lightconditions: 7 AM to 7 PM for the light period, 7 PM to 7 AM for the darkperiod. Chow and water: Free access to CRF-1 (Oriental Yeast Co, Ltd)and tap water.

Experimental Procedures

One day before each experiment, mice were weighed and randomized intoseveral groups in each test. On the morning of the experiment day, bodyweight was measured in order to calculate the administration volume ofeach animal. Vehicle, 7-OH-CBDV or CBDV was interperitoneallyadministered 30 minutes before electric stimuli. Maximal electroshockseizures (MES) in mice was induced by a stimulator (UGO BASILE ECT UNIT7801, Italia) using a current of 30 mA delivered with a pulse frequencyof 100 Hz for 200 msec through earlap electrodes. The mice were observedfor 10 seconds and the incidence of tonic hindlimb extension was noted.

Statistical Analysis

All statistical analyses were performed using SAS Software for Windows,Release 9.1. The difference of the number (hindlimb extension or deaths)in each group was assessed using two-tailed Fisher's exact test. Thedifferences were considered statistically significant, when the p valuewas less than 0.05.

Results

Table 2 below demonstrates that the data obtained for the 7-OH-CBDV wasstatistically significant when compared to vehicle. Similarly to theparent compound, CBDV, 7-OH-CBDV at both doses produced a decrease in90% of tonic clonic convulsions.

TABLE 2 Percentage decrease in tonic clonic convulsions Percentagedecrease in tonic clonic convulsions Compound (dose) compared withvehicle Vehicle — 7-OH-CBDV (150 mg/kg i.p.) 90% *** 7-OH-CBDV (200mg/kg i.p.) 90% *** CBDV (200 mg/kg i.p.) 82% *** *** - = p < 0.001

Conclusion

These data further demonstrate the surprising ability of the primarymetabolite of CBDV, 7-OH-CBDV to produce anti-convulsant effects.

References

-   Amada et al. (2013) Peer J, 2013, pages 1-18 “Cannabidivarin (CBDV)    suppresses pentylenetetrazole (PTZ)-induced increases in    epilepsy-related gene expression.”-   Ames F R and Cridland S (1986). “Anticonvulsant effects of    cannabidiol.” S Afr Med J 69:14.-   Carlini et al. (1981) Journal of Clinical Pharmacology, vol. 21, No.    8/9, 1981, pages 417S-427S “Hypnotic and antiepileptic effects of    cannabidiol.”-   Consroe P, Martin P, Eisenstein D. (1977). “Anticonvulsant drug    antagonism of delta-9-tetrahydrocannabinol induced seizures in    rabbits.” Res Commun Chem Pathol Pharmacol. 16:1-13-   Consroe P, Benedicto M A, Leite J R, Carlini E A, Mechoulam R.    (1982). “Effects of cannabidiol on behavioural seizures caused by    convulsant drugs or current in mice.” Eur J Pharmaco. 83: 293-8-   Cunha J M, Carlini E A, Pereira A E, Ramos O L, Pimental C,    Gagliardi R et al. (1980). “Chronic administration of cannabidiol to    healthy volunteers and epileptic patient.” Pharmacology. 21:175-85-   Hill et al. (2012) British Journal of Pharmacology, vol. 167, No. 8,    2012, pages 1629-1642 “Cannabidivarin is anticonvulsant in mouse and    rat.”-   Jones et al. (2012) Seizure, vol. 21, No. 5, 2012, pages 344-352    “Cannabidiol exerts anti-convulsant effects in animal models of    temporal lobe and partial seizures.”-   Mechoulam R and Carlini E A (1978). “Toward drugs derived from    cannabis.” Die naturwissenschaften 65:174-9.

The invention claimed is:
 1. A method of treating tonic-clonic seizures in a subject with epilepsy comprising administering a therapeutically effective amount of 7-hydroxy-cannabidiol (7-OH-CBD), thereby treating tonic-clonic seizures.
 2. The method of claim 1, wherein the 7-OH-CBD is in a pure, isolated or synthetic form.
 3. The method of claim 1, further comprising administering to the subject a therapeutically effective amount of 7-hydroxy-cannabidivarin (7-OH-CBDV).
 4. The method of claim 1, wherein the 7-OH-CBD is administered as a pharmaceutical composition comprising the 7-OH-CBD with a pharmaceutically acceptable carrier.
 5. The method of claim 1, further comprising administering to the subject one or more concomitant anti-epileptic drugs (AED).
 6. The method of claim 5, wherein the one or more AED is selected from the group consisting of: clobazam; levetiracetam; topiramate; stiripentol; phenobarbital; lacsamide; valproic acid; zonisamide; perampanel; and fosphenytoin.
 7. The method of claim 1, wherein the dose of 7-OH-CBD is between 1 and 2000 mg/kg.
 8. The method of claim 3, wherein the 7-OH-CBD is formulated for administration separately, sequentially or simultaneously with the 7-OH-CBDV or the combination is provided in a single dosage form.
 9. The method of claim 3, wherein the 7-OH-CBDV is in a pure, isolated or synthetic form.
 10. The method of claim 3, wherein the dose of 7-OH-CBDV is between 1 and 2000 mg/kg.
 11. The method of claim 4, wherein the pharmaceutical composition further comprises 7-hydroxy-cannabidivarin (7-OH-CBDV).
 12. A pharmaceutical composition comprising 7-hydroxy-cannabidiol (7-OH-CBD) with a pharmaceutically acceptable carrier.
 13. The pharmaceutical composition of claim 12, wherein the pharmaceutical composition further comprises 7-hydroxy-cannabidivarin (7-OH-CBDV).
 14. The pharmaceutical composition of claim 12, wherein the 7-OH-CBD is in a pure, isolated or synthetic form.
 15. The pharmaceutical composition of claim 12, wherein the composition is formulated to have a dose of 7-OH-CBD between 1 and 2000 mg/kg.
 16. The pharmaceutical composition of claim 13, wherein the 7-OH-CBD is formulated for administration separately, sequentially or simultaneously with the 7-OH-CBDV.
 17. The pharmaceutical composition of claim 13, wherein the 7-OH-CBD and 7-OH-CBDV are provided in a single dosage form.
 18. The method of claim 1, wherein the 7-OH-CBD is administered in an oral solution comprising the 7-OH-CBD and a pharmaceutically acceptable carrier.
 19. The method of claim 1, wherein the administering treats myoclonic jerks.
 20. The method of claim 1, wherein the administering reduces seizure severity.
 21. The method of claim 1, wherein the administering reduces latency to seizure onset. 